BACKGROUND: The urokinase plasminogen activator system has the potency to promote leukocyte recruitment and blood-CSF barrier breakdown, and thus may play an important pathophysiologic role in bacterial meningitis. METHODS: CSF and serum concentrations of urokinase-plasminogen activator (urokinase [uPA]), uPA receptor (uPAR), and PA inhibitor-1 (PAI-1) were quantified by ELISA in 12 patients with bacterial meningitis, control patients (n = 10) with noninflammatory neurologic diseases, and 10 patients with Guillain-Barré syndrome (GBS), a disease in which blood-CSF barrier disruption occurs without CSF pleocytosis. Casein zymography was used to determine PA-dependent plasminogen activation in the CSF. RESULTS: A marked increase in uPA-dependent plasminogen activation was detected in the CSF of patients with bacterial meningitis vs CSF of patients with GBS and controls. Accordingly, ELISA analysis of CSF revealed intrathecal upregulation of uPA protein in patients with bacterial meningitis. CSF concentrations of uPAR and PAI-1 were also elevated in these patients. The serum of patients with bacterial meningitis showed elevated protein levels of uPA, but not uPAR or PAI-1. Positive correlations were found between blood-CSF barrier breakdown and CSF uPA concentrations, and between CSF pleocytosis and CSF/serum ratios of the potent chemokine uPAR in patients with bacterial meningitis. Furthermore, an adverse clinical outcome in these patients correlated with serum uPA concentrations. CONCLUSION: In bacterial meningitis, the urokinase plasminogen activator system is involved in leukocyte recruitment and breaching of the blood-CSF barrier, and this may contribute to an unfavorable clinical outcome.
BACKGROUND: The urokinase plasminogen activator system has the potency to promote leukocyte recruitment and blood-CSF barrier breakdown, and thus may play an important pathophysiologic role in bacterial meningitis. METHODS:CSF and serum concentrations of urokinase-plasminogen activator (urokinase [uPA]), uPA receptor (uPAR), and PA inhibitor-1 (PAI-1) were quantified by ELISA in 12 patients with bacterial meningitis, control patients (n = 10) with noninflammatory neurologic diseases, and 10 patients with Guillain-Barré syndrome (GBS), a disease in which blood-CSF barrier disruption occurs without CSFpleocytosis. Casein zymography was used to determine PA-dependent plasminogen activation in the CSF. RESULTS: A marked increase in uPA-dependent plasminogen activation was detected in the CSF of patients with bacterial meningitis vs CSF of patients with GBS and controls. Accordingly, ELISA analysis of CSF revealed intrathecal upregulation of uPA protein in patients with bacterial meningitis. CSF concentrations of uPAR and PAI-1 were also elevated in these patients. The serum of patients with bacterial meningitis showed elevated protein levels of uPA, but not uPAR or PAI-1. Positive correlations were found between blood-CSF barrier breakdown and CSFuPA concentrations, and between CSFpleocytosis and CSF/serum ratios of the potent chemokine uPAR in patients with bacterial meningitis. Furthermore, an adverse clinical outcome in these patients correlated with serum uPA concentrations. CONCLUSION: In bacterial meningitis, the urokinase plasminogen activator system is involved in leukocyte recruitment and breaching of the blood-CSF barrier, and this may contribute to an unfavorable clinical outcome.
Authors: Barry B Mook-Kanamori; Madelijn Geldhoff; Tom van der Poll; Diederik van de Beek Journal: Clin Microbiol Rev Date: 2011-07 Impact factor: 26.132
Authors: Barry B Mook-Kanamori; Daan Fritz; Matthijs C Brouwer; Arie van der Ende; Diederik van de Beek Journal: PLoS One Date: 2012-09-13 Impact factor: 3.240
Authors: Martina L Sanderson-Smith; Yueling Zhang; Diane Ly; Deborah Donahue; Andrew Hollands; Victor Nizet; Marie Ranson; Victoria A Ploplis; Mark J Walker; Francis J Castellino Journal: PLoS Pathog Date: 2013-07-04 Impact factor: 6.823